The goal of this project is to characterize hepatitis E virus (HEV), to determine the extent and pattern of its involvement in enterically transmitted hepatitis, and to develop a vaccine for the prevention of hepatitis E.We identified and sequenced a hepatitis E virus that was ubiquitous in US swine and that was genetically divergent from other strains of HEV. Subsequently, two human cases of hepatitis E in the US yielded viruses very closely related to the swine HEV. We are examining sera from around the world and from other animal species in order to determine whether animal strains of HEV are widespread and, if so, what their genetic relationship is to each other and to human strains. We have shown that the majority of rats from 3 different geographical regions of the U.S. have antibody to HEV and thus rats may be a potential source of HEV infection in humans. We have purified a baculovirus-expressed recombinant capsid protein for additional vaccine studies in rhesus monkeys and have prepared material which was used for phase I clinical trials. A combinatorial phage Fab display library has been prepared from bone marrow cells of a chimpanzee that had been infected with HEV. Our recombinant HEV capsid protein was used to screen this library for monoclonal antibodies to HEV. Seventeen monoclonal antibodies were isolated and two are currently being tested for their ability to neutralize the virus. Since chimpanzee and human monoclonal antibodies are virtually identical, it should be possible to use such antibodies for passive immunoprophylaxis of humans if these immunoglobulins prove to exhibit a high level of neutralizing activity. - hepatitis E, animal reservoirs, monoclonal antibodies, rats, recombinant vaccine.